TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30241	90946;90947;90948	chr2:178552179;178552178;178552177	chr2:179416906;179416905;179416904
N2AB	28600	86023;86024;86025	chr2:178552179;178552178;178552177	chr2:179416906;179416905;179416904
N2A	27673	83242;83243;83244	chr2:178552179;178552178;178552177	chr2:179416906;179416905;179416904
N2B	21176	63751;63752;63753	chr2:178552179;178552178;178552177	chr2:179416906;179416905;179416904
Novex-1	21301	64126;64127;64128	chr2:178552179;178552178;178552177	chr2:179416906;179416905;179416904
Novex-2	21368	64327;64328;64329	chr2:178552179;178552178;178552177	chr2:179416906;179416905;179416904
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-108
• Domain position: 18
• Structural Position: 19
• Q(SASA): 0.1053
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
S/N	None	None	0.999	N	0.613	0.326	0.249502417897	gnomAD-4.0.0	1.59129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43312E-05	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
S/A	0.1388	likely_benign	0.1158	benign	-0.677	Destabilizing	0.998	D	0.505	neutral	None	None	None	None	N
S/C	0.112	likely_benign	0.1095	benign	-0.791	Destabilizing	1.0	D	0.806	deleterious	N	0.506475929	None	None	N
S/D	0.8873	likely_pathogenic	0.8125	pathogenic	-2.04	Highly Destabilizing	0.999	D	0.612	neutral	None	None	None	None	N
S/E	0.9099	likely_pathogenic	0.8458	pathogenic	-1.87	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
S/F	0.3804	ambiguous	0.3061	benign	-0.409	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
S/G	0.1712	likely_benign	0.1319	benign	-1.03	Destabilizing	0.999	D	0.555	neutral	N	0.498295947	None	None	N
S/H	0.5744	likely_pathogenic	0.5154	ambiguous	-1.485	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
S/I	0.5933	likely_pathogenic	0.4606	ambiguous	0.203	Stabilizing	1.0	D	0.811	deleterious	D	0.527947545	None	None	N
S/K	0.9734	likely_pathogenic	0.9469	pathogenic	-0.746	Destabilizing	0.999	D	0.607	neutral	None	None	None	None	N
S/L	0.3097	likely_benign	0.2303	benign	0.203	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
S/M	0.3224	likely_benign	0.275	benign	0.071	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
S/N	0.305	likely_benign	0.2472	benign	-1.433	Destabilizing	0.999	D	0.613	neutral	N	0.480596539	None	None	N
S/P	0.9953	likely_pathogenic	0.9894	pathogenic	-0.057	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
S/Q	0.8169	likely_pathogenic	0.7612	pathogenic	-1.176	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
S/R	0.9443	likely_pathogenic	0.9017	pathogenic	-1.059	Destabilizing	1.0	D	0.829	deleterious	N	0.498700794	None	None	N
S/T	0.151	likely_benign	0.1211	benign	-0.992	Destabilizing	0.999	D	0.543	neutral	D	0.523103549	None	None	N
S/V	0.5057	ambiguous	0.4097	ambiguous	-0.057	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
S/W	0.6126	likely_pathogenic	0.5493	ambiguous	-0.828	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
S/Y	0.3569	ambiguous	0.2869	benign	-0.379	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.